Age-related changes in the retina and retinal pigment epithelium (RPE) of pigmented rats have been characterized using morphological and biochemical techniques. One of the major age-related changes in the RPE is the progressive intracellular accumulation of lipofuscin, or age-pigment. Experiments were conducted to evaluate factors which may be involved in lipofuscin formation in the RPE. It was found that the amount of lipofuscin in the RPE is a linear function of the logarithm of dietary vitamin A levels. As reported previously, vitamin E deficiency accelerates lipofuscin accumulation in the RPE. We have found that the fluorescence emission spectrum of the pigment which accumulates in the RPE as a result of vitamin E deficiency is identical to that of the pigment which accumulates during aging. Our findings support the hypothesis that age-pigment in the RPE may be formed as the result of autoxidation of subcellular components, and that vitamin A makes a significant contribution to lipofuscin formation. The drug centrophenoxine has been reported to cause a decrease in lipofuscin content in a variety of tissues and is therefore a potentially useful tool for evaluating the role of lipofuscin accumulation in aging. We have found, however, that this drug has no apparent effect on RPE lipofuscin which has accumulated as a result of either aging or vitamin E deficiency.